A fusion analytic framework for investigating functional brain connectivity differences using resting-state fMRI.

Introduction: Functional magnetic resonance imaging (fMRI) data is highly complex and high-dimensional, capturing signals from regions of interest (ROIs) with intricate correlations. Analyzing such data is particularly challenging, especially in resting-state fMRI, where patterns are less identifiable without task-specific contexts. Nonetheless, interconnections among ROIs provide essential insights into brain activity and exhibit unique characteristics across groups. Methods: To address these challenges, we propose an interpretable fusion analytic framework to identify and understand ROI connectivity differences between two groups, revealing their distinctive features. The framework involves three steps: first, constructing ROI-based Functional Connectivity Networks (FCNs) to manage resting-state fMRI data; second, employing a Self-Attention Deep Learning Model (Self-Attn) for binary classification to generate attention distributions encoding group-level differences; and third, utilizing a Latent Space Item-Response Model (LSIRM) to extract group-representative ROI features, visualized on group summary FCNs. Results: We applied our framework to analyze four types of cognitive impairments, demonstrating their effectiveness in identifying significant ROIs that contribute to the differences between the two disease groups. The results reveal distinct connectivity patterns and unique ROI features, which differentiate cognitive impairments. Specifically, our framework highlighted group-specific differences in functional connectivity, validating its capability to capture meaningful insights from high-dimensional fMRI data. Discussion: Our novel interpretable fusion analytic framework addresses the challenges of analyzing high-dimensional, resting-state fMRI data. By integrating FCNs, a Self-Attention Deep Learning Model, and LSIRM, the framework provides an innovative approach to discovering ROI connectivity disparities between groups. The attention distribution and group-representative ROI features offer interpretable insights into brain activity patterns and their variations among cognitive impairment groups. This methodology has significant potential to enhance our understanding of cognitive impairments, paving the way for more targeted therapeutic interventions.